title: Siphonaxanthin, a marine carotenoid from green algae, effectively induces apoptosis in human leukemia (HL-60) cells.
abstract: BACKGROUND
  Bioactive marine molecules have recently received considerable attention for their nutraceutical characteristics. Considering the ever-increasing demand of nutraceuticals for anti-cancer therapy, we investigated the apoptosis-inducing effects of marine carotenoids, including siphonaxanthin, on human leukemia (HL-60) cells.
  
  
  METHODS
  Apoptotic effects were evaluated by cell viability assay, TUNEL assay, and caspase-3 activity. The expression of apoptosis-inducing death receptor-5 (DR5), Bcl-2 and Bax were assayed by Western blot analysis, and mRNA expression of GADD45α was assayed by quantitative RT-PCR analysis.
  
  
  RESULTS
  Siphonaxanthin potently inhibited the viability of HL-60 cells compared with the other carotenoids evaluated. In comparison with fucoxanthin, siphonaxanthin at a concentration of 20μM markedly reduced cell viability (p<0.05) as early as within 6h of treatment. The effective apoptotic activity of siphonaxanthin was observed by increases in TUNEL-positive cells, and by increased chromatin condensation in HL-60 cells. This induction of apoptosis was associated with the decreased expression of Bcl-2, and the subsequently increased activation of caspase-3. In addition, siphonaxanthin up-regulated the expression of GADD45α and DR5.
  
  
  CONCLUSIONS
  These data suggest that the dietary carotenoid siphonaxanthin could be potentially useful as a chemo-preventive and/or chemotherapeutic agent.
  
  
  CONCLUSIONS
  Our findings demonstrate for the first time the novel functional property of siphonaxanthin as a potent inducer of apoptosis in HL-60 cells.
authors.affiliation: Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Ponesakki
authors.initials: P
authors.lastname: Ganesan
authors.forename: Kenji
authors.initials: K
authors.lastname: Noda
authors.forename: Yuki
authors.initials: Y
authors.lastname: Manabe
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ohkubo
authors.forename: Yukihisa
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Maoka
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sugawara
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirata
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002338:Carotenoids / Q000737:chemistry / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D000460:Chlorophyta / Q000737:chemistry*; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008386:Marine Biology; D015394:Molecular Structure; D009687:Nuclear Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D024341:Xanthophylls / Q000737:chemistry / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000097642:GADD45 Proteins
chemical_list: D002338:Carotenoids; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D024341:Xanthophylls; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C003314:siphonaxanthin